Spisulosine

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 201300

CAS#: 196497-48-0

Description: Spisulosine, also known as ES-285, is novel compound derived from the marine mollusk Spisula polynoma with evidence of preclinical antitumor activity. Phase I clinical trial results: Dose level VIII (200 mg/m(2)) was considered the MTD, and dose level IX (160 mg/m(2)) was defined as the RD. Limited antitumor activity was observed.


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Spisulosine, purity > 98%, is not in stock, may be available through custom synthesis. Minimum 1 gram order is requested. Current shipping out time is about 70 days after order is received. Delivery time: overnight (USA/Canada); 3-5 days (worldwide). Shipping fee: $30.00 (USA); from $45.00 (Canada); from $70.00 (international).


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 201300
Name: Spisulosine
CAS#: 196497-48-0
Chemical Formula: C18H39NO
Exact Mass: 285.30316
Molecular Weight: 285.51
Elemental Analysis: C, 75.72; H, 13.77; N, 4.91; O, 5.60


Synonym: ES285; ES285; Spisulosine .

IUPAC/Chemical Name: (2R)-2-aminooctadecan-3-ol

SMILES Code: C[C@@H](N)C(O)CCCCCCCCCCCCCCC


Technical Data

Appearance:
Solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO, not in water

Shelf Life:
>5 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


Additional Information

Spisulosine (ES-285), isolated from the sea mollusc Spisula polynyma, in the prostate tumor PC-3 and LNCaP cell lines. Spisulosine inhibited cell proliferation with an IC50 of 1 microM in both cell lines, although it was more effective in the androgen-independent PC-3 cells. The anti-proliferative effect induced by Spisulosine in prostate cells was independent of peroxisome proliferator activated receptor gamma (PPARgamma) and phosphatidylinositol 3-kinase/(PI3K/Akt), Jun N-terminal kinase (JNK), p38 or classical protein kinase C (PKCs) pathways, as it was inferred from the results obtained with specific inhibitors of these routes. However, Spisulosine treatment of prostate cells induced an increase in the intracellular ceramide levels, that was totally blocked by the ceramide synthase inhibitor Fumonisin B1, indicating that the ceramide accumulation came from the de novo biosynthesis. Spisulosine also induced in both PC-3 and LNCaP cells, an activation of the atypical PKC isoform, PKCzeta, which is one of the target proteins of ceramide. These results indicate that the marine compound Spisulosine inhibits the growth of the prostate PC-3 and LNCaP cells through intracellular ceramide accumulation and PKCzeta activation. see: http://www.ncbi.nlm.nih.gov/pubmed/18343365.
  
 
 


References

1: Xu K, Lai G, Zha Z, Pan S, Chen H, Wang Z. A highly anti-selective asymmetric Henry reaction catalyzed by a chiral copper complex: applications to the syntheses of (+)-spisulosine and a pyrroloisoquinoline derivative. Chemistry. 2012 Sep 24;18(39):12357-62. doi: 10.1002/chem.201201775. Epub 2012 Aug 21. PubMed PMID: 22907874.

2: Massard C, Salazar R, Armand JP, Majem M, Deutsch E, García M, Oaknin A, Fernández-García EM, Soto A, Soria JC. Phase I dose-escalating study of ES-285 given as a three-hour intravenous infusion every three weeks in patients with advanced malignant solid tumors. Invest New Drugs. 2012 Dec;30(6):2318-26. doi: 10.1007/s10637-011-9772-8. Epub 2012 Jan 4. PubMed PMID: 22215532.

3: Chen BS, Yang LH, Ye JL, Huang T, Ruan YP, Fu J, Huang PQ. Diastereoselective synthesis and bioactivity of long-chain anti-2-amino-3-alkanols. Eur J Med Chem. 2011 Nov;46(11):5480-6. doi: 10.1016/j.ejmech.2011.09.010. Epub 2011 Sep 16. PubMed PMID: 21955681.

4: Malik G, Estéoule A, Retailleau P, Dauban P. Aziridines from intramolecular alkene aziridination of sulfamates: reactivity toward carbon nucleophiles. application to the synthesis of spisulosine and its fluoro analogue. J Org Chem. 2011 Sep 16;76(18):7438-48. doi: 10.1021/jo201209x. Epub 2011 Aug 24. PubMed PMID: 21812488.

5: Schöffski P, Dumez H, Ruijter R, Miguel-Lillo B, Soto-Matos A, Alfaro V, Giaccone G. Spisulosine (ES-285) given as a weekly three-hour intravenous infusion: results of a phase I dose-escalating study in patients with advanced solid malignancies. Cancer Chemother Pharmacol. 2011 Dec;68(6):1397-403. doi: 10.1007/s00280-011-1612-1. Epub 2011 Apr 5. PubMed PMID: 21465314.

6: Vilar E, Grünwald V, Schöffski P, Singer H, Salazar R, Iglesias JL, Casado E, Cullell-Young M, Baselga J, Tabernero J. A phase I dose-escalating study of ES-285, a marine sphingolipid-derived compound, with repeat dose administration in patients with advanced solid tumors. Invest New Drugs. 2012 Feb;30(1):299-305. doi: 10.1007/s10637-010-9529-9. Epub 2010 Sep 7. PubMed PMID: 20820909.

7: Baird RD, Kitzen J, Clarke PA, Planting A, Reade S, Reid A, Welsh L, López Lázaro L, de las Heras B, Judson IR, Kaye SB, Eskens F, Workman P, deBono JS, Verweij J. Phase I safety, pharmacokinetic, and pharmacogenomic trial of ES-285, a novel marine cytotoxic agent, administered to adult patients with advanced solid tumors. Mol Cancer Ther. 2009 Jun;8(6):1430-7. doi: 10.1158/1535-7163.MCT-08-1167. Epub 2009 Jun 9. PubMed PMID: 19509256.

8: Singh R, Sharma M, Joshi P, Rawat DS. Clinical status of anti-cancer agents derived from marine sources. Anticancer Agents Med Chem. 2008 Aug;8(6):603-17. Review. PubMed PMID: 18690825.

9: Sánchez AM, Malagarie-Cazenave S, Olea N, Vara D, Cuevas C, Díaz-Laviada I. Spisulosine (ES-285) induces prostate tumor PC-3 and LNCaP cell death by de novo synthesis of ceramide and PKCzeta activation. Eur J Pharmacol. 2008 Apr 28;584(2-3):237-45. doi: 10.1016/j.ejphar.2008.02.011. Epub 2008 Feb 14. PubMed PMID: 18343365.

10: Salcedo M, Cuevas C, Alonso JL, Otero G, Faircloth G, Fernandez-Sousa JM, Avila J, Wandosell F. The marine sphingolipid-derived compound ES 285 triggers an atypical cell death pathway. Apoptosis. 2007 Feb;12(2):395-409. PubMed PMID: 17191124.

11: Faircloth G, Cuevas C. Kahalalide F and ES285: potent anticancer agents from marine molluscs. Prog Mol Subcell Biol. 2006;43:363-79. Review. PubMed PMID: 17153351.

12: Den Brok MW, Nuijen B, García JL, Miranda E, Calvo P, Manada C, Beijnen JH. Compatibility and stability of the novel anticancer agent ES-285 x HCl formulated with 2-hydroxypropyl-beta-cyclodextrin in infusion devices. Pharmazie. 2006 Jan;61(1):21-4. PubMed PMID: 16454201.

13: Den Brok MW, Nuijen B, Meijer DM, Millán E, Manada C, Beijnen JH. Pharmaceutical development of a parenteral lyophilised formulation of the investigational anticancer agent ES-285.HCl. PDA J Pharm Sci Technol. 2005 Jul-Aug;59(4):246-57. PubMed PMID: 16218203.

14: Stokvis E, Rosing H, López-Lázaro L, Schellens JH, Beijnen JH. A more sensitive MS detector does not obviously lead to a more sensitive assay: experiences with ES-285. Biomed Chromatogr. 2004 Jul;18(6):403-7. PubMed PMID: 15273982.

15: den Brok MW, Nuijen B, Miranda E, Floriano P, Munt S, Manzanares I, Beijnen JH. Development and validation of a liquid chromatography-ultraviolet absorbance detection assay using derivatisation for the novel marine anticancer agent ES-285 x HCl [(2S,3R)-2-amino-3-octadecanol hydrochloride] and its pharmaceutical dosage form. J Chromatogr A. 2003 Dec 12;1020(2):251-8. Erratum in: J Chromatogr A. 2004 Apr 9;1033(1):191. PubMed PMID: 14661748.

16: Yun JM, Sim TB, Hahm HS, Lee WK, Ha HJ. Efficient synthesis of enantiomerically pure 2-acylaziridines: Facile syntheses of N-Boc-safingol, N-Boc-D-erythro-sphinganine, and N-Boc-spisulosine from a common intermediate. J Org Chem. 2003 Oct 3;68(20):7675-80. PubMed PMID: 14510541.

17: Maraschiello C, Miranda E, Millán E, Floriano P, Vilageliu J. Phenylisothiocyanate and dansyl chloride precolumn derivatizations for the high-performance liquid chromatography analysis of the antitumoral agent ES-285 in dog plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Jul 5;791(1-2):1-11. PubMed PMID: 12798159.

18: Stokvis E, Nan-Offeringa L, Rosing H, López-Lázaro L, Aceña JL, Miranda E, Lyubimov A, Levine BS, D'Aleo C, Schellens JH, Beijnen JH. Quantitative analysis of ES-285, an investigational marine anticancer drug, in human, mouse, rat, and dog plasma using coupled liquid chromatography and tandem mass spectrometry. J Mass Spectrom. 2003 May;38(5):548-54. PubMed PMID: 12794877.

19: Cuadros R, Montejo de Garcini E, Wandosell F, Faircloth G, Fernández-Sousa JM, Avila J. The marine compound spisulosine, an inhibitor of cell proliferation, promotes the disassembly of actin stress fibers. Cancer Lett. 2000 Apr 28;152(1):23-9. PubMed PMID: 10754202.